We are studying the organization and development of bilateral optic projections in normal mice and in pigmentation mutants, by using and developing morphological and physiological tools. Pigmentation defects correlate not only with faulty partial decussations but also with defects in eye movements and light sensitivity. --With monoclonal antibodies against phosphorylated sites on the heavy neurofilament (NF) subunit, in combination with optic tract lesions, we can selectively label a subpopulation of ganglion cells that has a line of descussation at the midline representation. We will test the impression that these are the cells that are most severely affected in pigmentation mutants, and we will search for morphological correlates of the eye movement defect. By combining the NF-markers with thymidine labeling we will test whether the neurofilamentous ganglion cells are the earliest population formed. --As protein phosphorylation is a major biochemical mechanism for the execution of changes, the NF antibodies can be used to detect functional changes. Such antibodies demonstrate subtle damage in the aging brain which cannot be detected with conventional histological methods, changes due to contact with neurotoxic substances, and abnormalities in otherwise normal neurons in the mutant mouse pcd. We are trying to understand the mechanisms underlying these changes in phosphorylated NF's, and we will test the impression that they reflect regenerative attempts of the neurons. --NF- and related antibodies can detect very rapid light-induced changes: so far, we found two antibodies selective for illuminated and one for dark-adapted photoreceptor outer segments; one of them crossreacts with phosphorylated rhodopsin. We will test the physiological criteria (dark-adaptation, light-intensity functions) of the light- and dark-activated antigens, and we will search for a correlate of the light-sensitivity defect in pigmentation mutants. --With a method that seems to selectively label dying ganglion cells in the newborn mouse, we will study the errors in the formation of the bilateral optic projections. --Finally, we will study normal and albino embryos at early stages of eye development using methods we have already in hand (e.g. antibodies against mitotic cells, early differentiating neurons, early pigment epithelium), and we hope to develop others, in order to search for early effects of the albino mutation.